tbuckley/cabot-search huggingface dataset:
BIOM-03. COMPREHENSIVE GENOMIC AND IMMUNE PROFILING OF NON-SMALL CELL LUNG CANCER BRAIN METASTASES REVEALS LOW TUMOR INFLAMMATION AND ELEVATED CANCER TESTIS ANTIGEN BURDEN
Authors: R J Seager, Sarabjot Pabla, B R Achyut, Mary Nesline, Geoffrey Kannan, Anjen Chenn, Shengle Zhang, Roger Klein, Jeffrey Conroy, Mark Sausen, Kamal Saini, Taylor Jensen, Prasanth Reddy, Eric Severson, Shakti Ramkissoon
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Non-small cell lung cancer (NSCLC) accounts for ~50% of brain metastases. We present the genomic and immune biomarker landscape for a cohort with metastatic NSCLC to the brain. METHODS We analyzed brain metastases FFPE tissue (n=137; ages 40-85y (mean 65y), 52% female, 48% male) vs. primary sites (n=5533; ages 24-100+y (mean 71y), 51% female, 49% male) for advanced or metastatic NSCLC patients with comprehensive genomic and immune biomarker profiling, including PD-L1 IHC, tumor mutational burden (TMB), Tumor Immunogenic Signature (TIGS), Cell Proliferation (CP), and Cancer Testis Antigen Burden (CTAB). RESULTS Genomic alteration (GA) frequency for NSCLC brain metastasis versus primary sites were similar among the most frequently mutated genes except for KRAS which was significantly higher among brain metastases (39.9% vs 25.5%, p&amp;lt; 0.0005). No significant differences were observed for TP53 (50.7% vs 50.2%), STK11 (11.5% vs 10.9%), CDKN2A (10.1% vs 7%), or EGFR (8.0% vs 11.5%). PD-L1 expression for all cases by IHC was not significantly different (mean TPS 29.9% vs 26.3%); however, brain metastases were more likely to be PD-L1 negative (TPS&amp;lt; 1%) (46.3% vs 33.3%, p&amp;lt; 0.005). Conversely, TMB was higher in brain metastases versus primary sites (12.9 vs 10.2 muts/MB, p&amp;lt; 8x10-10), with more TMB-high cases (10 muts/Mb) (57.0% vs 33.5%, p&amp;lt; 3x10-8). Similarly, brain metastases had a higher proportion of CTAB-high cases (68.6% vs 57.6%, p=0.01). The immune response biomarker score, TIGS, was more often weak in brain metastases (52.6% vs 34.0%, p&amp;lt; 9x10-6). CONCLUSION In NSCLC, metastatic brain lesions have a larger antigen burden, with increased TMB and CTAB, likely due to the immune privileged nature of the brain, which is reflected in the lower TIGS scores and PD-L1 positivity. Despite lower PD-L1 positivity, NSCLC brain metastases with negative PD-L1 IHC may potentially benefit from immunotherapy strategies given the high TMB and CTAB.
NCMP-10. NEURO-OPHTHALMOLOGICAL FINDINGS IN CHILDREN AND ADOLESCENTS WITH MEDULLOBLASTOMA - A RETROSPECTIVE ANALYSIS
Authors: Maria Aliotti Lippolis, Sabine Koinig, Amedeo Azizi, Christian Dorfer, Berthold Pemp
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND Medulloblastoma represents the most common malignant pediatric brain tumor. Ophthalmic complications are possible sequelae. METHODS Pediatric medulloblastoma (MB) patients treated at the Medical University of Vienna from January 2012 to August 2021 were analyzed and their last ophthalmic assessment was reviewed. RESULTS Fifty-six MB patients could be included (71.4% non-WNT/non-SHH, 16.1% SHH-activated, 8.9% WNT-activated, 3.6% non-specified). Mean age at diagnosis was 7.2 years (range 0-19). Median follow-up to last ophthalmological assessment was 19.7 months (range 0.1-93.2). Thirty-four children underwent tumor resection at our hospital, their tumor localizations were: vermis (55.9%), floor of the 4th ventricle (26.5%), cerebellar hemispheres (11.8%), lateral recess (5.9%). Symptoms at presentation were evaluable for 51 children: 92.2% had symptoms of elevated intracranial pressure, 76.5% ataxia and 21.6% visual disturbances. Postoperative posterior fossa syndrome was observed in 11.1% of 54 children. 98.2% had chemotherapy as part of their initial treatment and all children older than four years (85.7%) received postoperative irradiation of the posterior fossa. In 13 (23.2%) intraventricular chemotherapy was applied. At the last follow-up 21 patients experienced relapse after primary treatment. At the final assessment, frequent neuro-ophthalmological abnormalities included: oculomotor disturbance (75%), esotropia (35.7%) including abducens palsy (12.5%), other cranial nerve palsies (21.4%), horizontal gaze-evoked nystagmus (51.8%), spontaneous nystagmus (16.1%), ocular tilt reaction (21.4%), and optic disc abnormalities (14.3%). Good visual acuity (≥20/25) was maintained in 62.5% patients. Visual field and optical coherence tomography was successfully performed in 75% and 66.1% of patients, respectively. Optic pathway lesions were detected in 4 patients (7.1%), including two cases with occipital metastases, one with optic nerve metastasis and one with leptomeningeal carcinomatosis. Orthoptic treatment with prisms and strabismus surgery was required in 14.3% and 7.7% of children, respectively. CONCLUSION Children with MB frequently suffer from neuro-ophthalmological late-effects. Regular monitoring is warranted to initiate appropriate management.
NIMG-53. DELTA RELAXOMETRY WITH CONTRAST ENHANCED MAGNETIC RESONANCE FINGERPRINTING: INITIAL APPLICATION TO DIFFERENTIATE BRAIN METASTASES AND GLIOBLASTOMA
Authors: Shengwen Deng, Walter Zhao, Abraham Nirappel, David Jordan, Andrew Sloan, Dan Ma, Chaitra Badve
Journal: Neuro-Oncology (2022)

Abstract PURPOSE The utility of post-contrast magnetic resonance fingerprinting (MRF) for brain tumor assessment has not been assessed. The aim of this work is to report differences in MRF-derived delta-relaxometry metrics between brain metastases and glioblastoma, offering a new strategy for tumor differentiation. METHODS Post- and pre-contrast MRF (T1, T2 and proton density maps) were acquired from 29 patients (14 brain metastases (Met), 15 glioblastoma (GB)) along with conventional MRI (T1w, T1w-Gd, T2w, T2w-FLAIR, and ADC). Post-contrast MRF was skull-stripped and non-linearly co-registered with pre-contrast MRF. Delta relaxometry metrics (ΔR1/ΔR2 ratio, ΔR1, ΔR2, and normalized ΔR1/ΔR2) were calculated in the native image space (1.2x1.2x3.0 mm3). Tumor regions were segmented using DeepMedic into necrotic core (NC), enhancing tumor (ET), and peritumoral edema (ED). ROI-averaged means of delta relaxometry metrics were compared using paired t-test for ET and ED regions in Met vs GB. Voxel-wise ΔR1/ΔR2 ratios (log transformed) were compared using unpaired two-tailed t-test with Bonferroni correction to quantify distribution differences in delta relaxometry between Met and GB. RESULTS Across all voxels of all patients in each group, ΔR1/ΔR2 ratios between Met and GB were different (0.272±0.61 vs 0.247±0.66 in ED, p &amp;lt; .001; 0.278±0.69 vs 0.264±0.67 in ET, p &amp;lt; .001). On a per-patient basis, the median, 75th percentile, and 90th percentile of ΔR1/ΔR2 ratios were different between ET and ED regions (p &amp;lt; .001). Within-ROI (NC, ET, and ED) averaged mean ΔR1/R2 ratios were not significantly different between Met and GB. CONCLUSION Voxel-wise distribution of ΔR1/ΔR2 ratios was different between tumor types (Met and GB) in both ET and ED regions. ROI-averaged ΔR1/ΔR2 ratios were different between ET and ED regions, but not specific for tumor type. Delta relaxometry provides a unique tumor-specific contrast and shows potential for solid tumor as well as peritumoral edema differentiation between Met and GB.
NIMG-110. FIRST CLINICAL EXPERIENCE WITH BELZUTIFAN IN VON HIPPEL-LINDAU DISEASE-ASSOCIATED CNS HEMANGIOBLASTOMA
Authors: Andrew Dhawan, David Peereboom, Glen Stevens
Journal: Neuro-Oncology (2022)

Abstract The authors present two cases of von Hippel-Lindau (VHL) disease-associated hemangioblastomas in the central nervous system (CNS) treated with the newly-approved HIF-2α inhibitor, belzutifan. The first case is that of a 31-year-old female with confirmed pathogenic germline VHL mutation who presented with multiple hemangioblastomas diagnosed at 25 years of age. The patient was first managed surgically with resection of three posterior fossa hemangioblastomas but re-presented five years later with headaches and paresthesias of the fingers. She was found to have interval progression of an intramedullary cervical lesion that was monitored radiographically, as well as a new cerebellar lesion. A cerebellar lesion was resected, but the cervical hemangioblastoma was not. Four months after surgery, the patient was started on belzutifan, which she tolerated without issue, and a brisk reduction in peri-lesional edema was observed in the cervical spine and remaining intracranial foci after 2 months of treatment. The second patient is a 30-year-old male with familial VHL disease, initially diagnosed after the discovery of a retinal hemangioblastoma at age 10. He was found to have multiple cerebellar hemangioblastomas, treated with resection at age 24 and then with stereotactic radiosurgery (SRS) at age 25, complicated by radiation necrosis. Imaging surveillance revealed disease progression at age 29 for which he was started on belzutifan. Follow-up imaging after three one month cycles revealed a reduction in perilesional edema and reduced lesion mass effect. Both patients tolerated belzutifan well, with only anemia and fatigue. We highlight in this report our initial experience and early imaging findings associated with belzutifan used for VHL disease-associated CNS hemangioblastomas.
NIMG-89. DISSEMINATED SPINAL METASTASES FROM A PITUITARY CARCINOMA
Authors: Mark Anderson, Parakash Pratibhu
Journal: Neuro-Oncology (2022)

Abstract Pituitary carcinomas are rare malignant neoplasms and rarely result in a solitary spinal metastasis. In this report we describe a case of pituitary carcinoma that metastasized to the spinal canal and the nerve roots at numerous spinal levels, mimicking neurofibromatosis of the spine. This patient is a 72 year old right-handed female with past medical history of pituitary adenoma which was resected 5 years prior and stable on imaging. At presentation, patient was seen for right sciatica, and an MRI showed multiple enhancing intradural extramedullary lesions mainly in the lumbar spine, felt to represent nerve sheath tumors, neurofibromas. She underwent genetic testing, but NF1, NF2, SMARC1B, SPRED1, LTRZ1 were not found to have a mutation. Over a 3 year period, she had progression of her spinal tumors. The pituitary lesion remained stable in appearance. She underwent resection of multiple lumbar lesions and pathology was consistent with pituitary carcinoma.Patient tolerated up to almost 11 full cycles of temozolomide before it was put on hold due to significant deconditioning and lethargy. Imaging revealed a partial response of the spinal cord metastases. This is an unusual presentation for metastatic pituitary carcinoma and delay in diagnosis resulted in significant morbidity.
RADT-26. PATTERNS OF RECURRENCE IN PATIENTS TREATED WITH RE-IRRADIATION FOR RECURRENT HIGH-GRADE GLIOMA
Authors: Debanjali Datta, Archya Dasgupta, Lilawati Meena, Abhishek Chatterjee, Arpita Sahu, Amit Chaudhari, Kishore Joshi, Ameya Puranik, Venkatesh Rangarajan, Vikas Singh, Prakash Shetty, Aliasgar Moiyadi, Nandini Menon, Vijay Patil, Ayushi Sahay, Epari Sridhar, Rajesh Kinhikar, Tejpal Gupta
Journal: Neuro-Oncology (2022)

Abstract Purpose/Objective(s) Re-irradiation (ReRT) is often used to treat recurrent high grade glioma (HGG). There is limited literature regarding the patterns of recurrence following ReRT, which was investigated in the current study. Materials/METHODS Patients with available radiation (RT) contours, dosimetry, and imaging-based evidence of recurrence were included in the retrospective study. All patients were treated with fractionated RT using conformal technique. Recurrence was documented as per decision in tumor board based on imaging with magnetic resonance imaging (MRI) or Flouroethyl-L-Tyrosine (FET) positron emission tomography (PET), which was registered with the planning CT. Failure patterns were classified as in-field, marginal, and out-field as decided by &amp;gt;50% recurrence volume within 95%, 20-95%, and outside 20% isodose lines, respectively. RESULTS Study population included 37 patients treated with median dose of 54 Gy (range 50.4-54 Gy). Before ReRT, 92% patients had undergone surgery (biopsy in 3, gross total resection in 9, subtotal resection in 22), 62% received concurrent chemo with ReRT, and 49% received maintenance chemotherapy. Median time to recurrence was 9 months (7-16 months, median 10 and 8 months respectively for in-field and marginal/out-field recurrence). In-field, marginal, and out-field recurrence were seen in 24 (65%), 10 (27%), and 3 (8%), respectively. Recurrence mapping was done using MRI, PET, or both in 27, 3, and 7, respectively. Of 24 patients with in-field recurrence, 8 and 16 had disease volume within gross tumor volume and clinical target volume, respectively. 2 patients had leptomeningeal dissemination (1 with majority of recurrence volume in-field and 1 with marginal failure in addition to metastatic disease). CONCLUSION Following ReRT for HGG, the majority of recurrence was in the high dose region, suggesting the use of conservative target volumes. Future studies are required for feasibility of dose-escalation to improve control rates, particularly in patients with long intervals from first course of RT.
NIMG-36. MR PERFUSION IS A BETTER PREDICTOR OF TUMOR RECURRENCE AND TREATMENT RESPONSE THAN STANDARD MRI IN SOME OLIGODENDROGLIOMA PATIENTS
Authors: Jennifer Connelly, Melissa Prah, Kathleen Schmainda
Journal: Neuro-Oncology (2022)

Abstract Dynamic susceptibility contrast (DSC) perfusion MRI (pMRI) has proven efficacy in the evaluation of glioma grade, progression and response to therapy. While not currently integrated within RANO (Response Assessment in Neuro Oncology) criteria, pMRI is often assessed alongside standard imaging of astrocytic glioma. In contrast, evaluation of pMRI in oligodendroglioma, has been less well-studied despite its potential to evaluate the comparatively greater vascularity of its “chicken-wire” capillary networks. Moreover, standard imaging to evaluate oligodendroglioma course can be confounded by slow-growing enhancement that does not meet RANO threshold for progression, or disease control despite low or absent radiographic response, and radiation-induced leukoencephalopathy resembling hyperintense changes on T2w and FLAIR imaging. Consequently, there is a clinical need to understand the potential role of pMRI in the evaluation of oligodendroglioma. As an initial step, we present here a case study of a patient with oligodendroglioma for which pMRI bested standard imaging in evaluation throughout radiographic disease surveillance. A 32 y/o gentleman with oligodendroglioma WHO grade 2 (IDH mutant, 1p19q codeletion) completed standard treatment, including surgical resection, irradiation, and chemotherapy. During surveillance imaging, a region of hyperperfusion on pMRI developed. However, since standard imaging was stable, RANO criteria was not met and observation was continued without intervention. Subsequent standard imaging demonstrated clear radiographic progression, reflecting the radiographic findings of pMRI but with delayed manifestation. Systemic chemotherapy was resumed with successively stable standard MR imaging. In contrast, the previous region of hyperperfusion improved over serial pMRI, and more consistently mirrored the patient’s clinical course. This case illustrates the timely radiographic importance of pMRI in assessing stability of tumor as well as treatment response. Considerations for the inclusion of pMRI within RANO criteria should be explored further.
PATH-47. THE CHALLENGE AND THERAPEUTIC RELEVANCE OF A NON-MATCHING CLASSIFIER OUTPUT USING GENOME-WIDE DNA METHYLATION FOR CLINICAL ROUTINE
Authors: Richard Drexler, Alicia Eckhardt, Helena Bode, Krystian Fita, Katrin Lamszus, Manfred Westphal, Lasse Dührsen, Ulrich Schüller, Malte Mohme
Journal: Neuro-Oncology (2022)

Abstract DNA methylation-based classification of central nervous system tumours has been increasing in importance for routine clinical workups and offers novel opportunities in discriminating subtypes which could lead to a more customized therapy. However, there are still unclassifiable entities for which defining an effective therapeutic regimen is challenging. The aim of our study was to gain further insight in these challenging cases. We included 81 patients with a calibrated score below 0.9 in the classifier output, who underwent surgery for a tumour of the central nervous system (CNS). 47 patients had a different output using the classifier version v11b4 when compared to their histological diagnosis. Of these, 41 patients (87.2 %) did not have any diagnosis from the methylation classifier (“no matching methylation class”). Surgical and clinicopathological features as well as DNA input had no impact on the calibrated score. Cases with non-classifiable tumors had a significantly longer time until a decision for adjuvant therapy and these cases were presented more often in neurooncological tumor boards (p&amp;lt; 0.01). Further analyses in 23 glioblastoma patients revealed comparable results for the overall survival, but a significantly shorter progression-free survival in cases with a discrepancy between the histological and classifier diagnosis. Application of the latest classifier version v12.5 enabled classification in 67.9% of cases, resulting in re-classification with a high calibrated score (&amp;gt; 0.9) in 25.7% of the tumors. Taken together, our study presents unclassifiable cases and the possible clinical impact when waiting for the accurate diagnosis in these challenging cases. Even though DNA methylation profiling significantly contributes to advanced CNS tumour diagnostics, clinicians should be aware of a prolonged interval to treatment initiation, especially for highly malignant brain tumours. Therefore, we would recommend to schedule adjuvant treatment as early as possible if surgical and histological results are suspicious for this disease.
RADT-02. IMPACT OF SINGLE AND DUAL IMMUNE CHECKPOINT BLOCKADE ON RISK OF RADIATION NECROSIS AND LOCAL CONTROL AMONG PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Eugene Vaios, Rachel Shenker, Peter Hendrickson, Rachel D'Anna, Donna Niedzwiecki, David Carpenter, Warren Floyd, Sebastian Winter, Jorg Dietrich, April Salama, Jeffrey Clarke, Karen Allen, Trey Mullikin, Scott Floyd, John Kirkpatrick, Zachary Reitman
Journal: Neuro-Oncology (2022)

Abstract PURPOSE Single and dual immune checkpoint inhibition (ICPI) are common treatment options for patients, particularly with melanoma and non-small cell lung cancer (NSCLC). While data suggest a cancer control benefit of combining stereotactic radiosurgery (SRS) and ICPI, we hypothesized that concurrent dual ICPI and SRS increases risk for radiation necrosis (RN). METHODS We retrospectively reviewed patients with metastatic melanoma or NSCLC treated with SRS for intact brain metastases from 2014-2020. Patients were stratified by receipt of dual ICPI, single ICPI, and SRS alone. Concurrent ICPI was defined as treatment within 30 days of SRS. RN and local control (LC) were biopsy confirmed or determined radiographically and longitudinally, in combination with clinical assessment and steroid use. Kaplan-Meier estimates were used to compare rates of RN and LC between cohorts. RESULTS 673 brain lesions from 93 patients met inclusion criteria [median (Q1, Q3): 5.0 (2.0-10.0) lesions per patient]. Median follow-up was 8.1 months (95% CI: 7.3-8.7). Histologies included melanoma (53.5%), adenocarcinoma NSCLC (27.3%), squamous cell NSCLC (6.1%), and NSCLC NOS (6.1%). 88 lesions from 25 patients (27%) developed RN and 11 (13%) were biopsy-proven. ICPI use was enriched among lesions that developed RN (85.2%) versus those that did not (19.8%). RN was associated with concurrent ICPI (p&amp;lt; 0.001). Freedom from RN at 6 months was 80% for dual ICPI, 82% for single ICPI, and 97% for SRS alone; 12-month rates were 78% in each ICPI cohort and 95% with SRS alone (p=0.0002). LC differed among dual (97.5%), single (88.7%), and no ICPI (79.7%, p &amp;lt; 0.001). There was a trend toward improved LC with RN (96.6% vs 91.8%; p=0.087). CONCLUSIONS In a large cohort of brain metastases, we observed increased risk of RN and improved LC with SRS plus concurrent dual or single ICPI. Awareness of these associations is critical for patient management.
CNSC-25. METABOLISM ACROSS BRIDGE OF SIGHS TO ONCOHISTONES
Authors: Sasi S.Senga
Journal: Neuro-Oncology (2022)

Abstract Brain tumours continue to be one of the leading causes of childhood mortality related to cancers. Oncohistones such as H3K27M, and H3G34R mutations have been linked to childhood brain tumours. The reason for the incidence of Oncohistone mutation in a developmental setting provides some novel insight for better therapeutics. The maintenance of the progenitor state might be driven by metabolism dictated Oncohistone mutations at the expense of differentiation in the developing brain paving way for tumourigenesis. I propose methods to target metabolic disturbances in the developing brain even prior to the rise of such somatic oncohistone mutations. Additionally, I provide insight into the reason for selective co-mutations that occur with specific Oncohistones in childhood brain tumours providing a rationale for effective therapeutics. In 2021, I proposed neuronal signalling as an Hallmark of cancer, in the context of childhood brain tumours, the nervous system functions as a fulcrum between metabolic reprogramming and the rise of oncohistone mutations leading to epigenetic reprogramming. The nervous system is a lucrative target in inhibiting the metabolic cues that support oncohistones. Metabolic reprogramming may underpin epigenetic reprogramming driving the developing brain across the Bridge of Sighs towards tumourigenesis.
NCMP-16. UNIQUE PARANEOPLASTIC SYNDROME ASSOCIATED WITH CLL
Authors: Catherine Boldig, Mark Warman, Neha Verma, Sepideh Mokhtari
Journal: Neuro-Oncology (2022)

Abstract Chronic lymphocytic leukemia is a hematologic malignancy characterized by overproduction of monoclonal B cells. Most people diagnosed with CLL do not immediately undergo treatment due to treatment guidelines. There are few cases of paraneoplastic syndrome associated CLL. This case is unique in that it is a paraneoplastic KLHL 11 antibody associated CLL. The patient is a 68-year-old female who originally presented to the hospital with abdominal pain and upon further imaging was found have retroperitoneal lymphadenopathy. After further studies including flow cytometry, she was diagnosed with CLL. She failed trials of Pembrolizumab, ibrutinib, and Obinutuzumab due to side effects. The patient then started experiencing excessive fatigue, bilateral temporal headache, nausea, vomiting, vertigo, tremor of bilateral upper extremities, and head bobbing. Her brain imaging was negative for acute abnormalities. Lumbar puncture was positive for CLL cells and the paraneoplastic panel came back positive with KLHL 11 antibodies. The patient’s symptoms continued to persist and her tremor and dysmetria continued to worsen. Due to the positive paraneoplastic panel, the patient was started on intravenous immunoglobulin but did not experience improvement. She was then trialed on intravenous methylprednisolone and still experienced no relief. She then underwent plasma exchange. Finally, she was given rituximab infusions with slight improvement. Her imaging remained negative for signs of leptomeningeal enhancement. Given the patient’s symptoms, negative brain imaging, and positive paraneoplastic panel, it was determined that the patient developed an irreversible paraneoplastic syndrome related to her CLL versus possible leptomeningeal disease. There are a few cases of paraneoplastic syndrome associated CLL involving paraneoplastic phemphigus, hypercalcemia, and nephrotic syndrome. This case is unique in that her symptoms presented with an ataxic syndrome with positive KLHL11 antibodies. It is important to be aware that some cases of CLL can present with unique paraneoplastic syndromes.